clonazepam

General Information

Clonazepam (brand Klonopin) is a high-potency, long-acting benzodiazepine approved for seizure disorders (1975) and panic disorder (1998). In psychiatric practice it is used off label for catatonia, acute agitation, or short-term augmentation of severe anxiety while primary therapies take effect.

Its 30–40 hour half-life provides sustained coverage but leads to accumulation in older adults or hepatic impairment. Tablets and orally disintegrating tablets (0.5 mg, 1 mg, 2 mg) can be swallowed or administered sublingually when rapid absorption is required. Dependence risk mandates clear treatment goals and taper plans for every course.

The clonazepam compare view, clonazepam evidence feed, and clonazepam print page can support shared decision-making and take-home counseling; the schizophrenia hub and bipolar disorder hub include catatonia and agitation workflows.

Schedule IV status reflects misuse potential. It is often reserved for targeted indications, with frequent reassessment; counseling commonly focuses on dependence/withdrawal risk and impaired driving risk.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Positive allosteric modulator of GABA-A receptors that increases GABA affinity and chloride channel opening, enhancing inhibitory neurotransmission.

High intrinsic potency (~0.5 mg clonazepam equals ~10 mg diazepam) means small dose changes can produce large effects and heighten overdose risk when combined with other sedatives.

• Facilitates GABA-A receptor function; no intrinsic activity without endogenous GABA.
• Minimal direct activity at serotonergic, dopaminergic, or adrenergic receptors.

Metabolism and Pharmacokinetics

• Oral bioavailability ~90% with peak concentrations 1–4 hours post dose; highly lipophilic with rapid CNS penetration.
• Metabolized primarily via CYP3A to inactive metabolites; elimination half-life averages 30–40 hours (can extend to 60 hours in older adults or hepatic impairment).

Dosing and Administration

• Panic disorder (label): start 0.25 mg twice daily; increase every 3 days to 1 mg twice daily; maximum 4 mg/day.
• Catatonia or acute agitation (off label): 0.5–1 mg orally or sublingually every 8–12 hours with daily reassessment; taper once stabilized.
• Seizure disorders (label): initiate 0.5 mg three times daily, increasing by 0.5–1 mg every 3 days; maximum 20 mg/day.
• Reduce initial doses in older adults, hepatic impairment, respiratory disease, or when co-prescribing other CNS depressants. The largest portion is often scheduled at bedtime, and taper planning is typically addressed before initiation.

Monitoring & Labs

• Sedation, cognition, gait/ataxia, and fall risk at each visit; counseling commonly covers driving and occupational safety after dose changes.
• Respiratory risk (sleep apnea, COPD) and co-prescribed CNS depressants; overdose education is important, and some settings coordinate naloxone when opioids are unavoidable.
• Misuse/diversion risk: PDMP review, documentation of indication/duration, and periodic reassessment with a time-limited plan are common.
• Withdrawal risk: written taper schedules, tracking rebound anxiety/insomnia, and slower tapers for long-term users or higher doses are typical.

Clonazepam monitoring is centered on safety (sedation/respiratory depression), dependence risk, and structured tapering rather than routine laboratory surveillance.

Adverse Effects

Interactions

• Additive CNS and respiratory depression with opioids, alcohol, antihistamines, or antipsychotics; combinations are generally avoided, and overdose education is important.
• CYP3A inhibitors (ketoconazole, clarithromycin, ritonavir) increase clonazepam exposure—reduce dose and monitor for oversedation.
• CYP enzyme inducers (carbamazepine, phenytoin, rifampin, St. John’s wort) may lower clonazepam levels—adjust doses based on clinical response.

Other Useful Information

• Expectations for time-limited use and taper plans are commonly documented at initiation.
• For catatonia, daily reassessment is typical; when response is inadequate, protocols often escalate to a lorazepam challenge or electroconvulsive therapy.
• Prescription monitoring data review and screening for substance use disorders are common at follow-up encounters.
• Patient counseling often includes the need for gradual tapering (avoiding abrupt discontinuation) and to report emergent cognitive changes or imbalance.

References

1. Klonopin (clonazepam) prescribing information — DailyMed (2025)
2. Evidence Based Pharmacological Treatment OF Anxiety Disorders — Depression and Anxiety (2014)
3. Benzodiazepines FOR Catatonia: Systematic Review AND Meta Analysis — Schizophrenia Research (2018)
4. ASAM guideline on benzodiazepines — Journal of Addiction Medicine (2020)
5. Evidence Based Consensus Guidelines FOR THE Management OF Catatonia: Recommendations From THE British Association FOR Psychopharmacology — Journal of Psychopharmacology (2023)